ABSTRACT Background: Sickle cell disease (SCD) is the most common genetic blood disorder in the United States (US) and Jamaica and primarily affects individuals of African descent. SCD can result in severe and debilitating complications, including vaso-occlusive crises and organ damage. To prevent these complications SCD requires complex self-management. SCD is associated with significantly shortened lifespans in both countries; however the average lifespan in Jamaica is 10.5-11 years longer when compared to the US. Many personal and background factors including, perceived stigma, demographics (country, age, race, sex, socioeconomic status) and clinical (disease severity, hydroxyurea use, genotype) characteristics may influence self- management strategies and QoL in SCD. These characteristics have not been explored in either country and there are many differences between countries in how SCD is managed and stigma is perceived. Methods: This cross sectional study will utilize a convergent parallel mixed methods design (individual interviews and self-report surveys). Participants will be interviewed about disease self-management strategies and how sources of stigma influence these strategies. Demographic and clinical characteristics will be assessed using questionnaires. Quantitative measures will be used to assess perceived stigma [SCD Health- Related Stigma Scale (SCD-HRSS)] and QoL [Adult Sickle Cell Quality of Life Measures (ASCQ-Me) emotional impact, pain episodes, pain impact, sleep impact, social functioning impact, and stiffness impact; disease severity]. The specific aims of this study are to: Aim 1: Determine the influence of perceived stigma and demographic and clinical characteristics on SCD self- management and QoL in adults with SCD in the US and Jamaica. Question 1: What are the influences of perceived stigma and demographic and clinical characteristics on SCD self-management? Question 2: What are the influences of perceived stigma and demographic and clinical characteristics on QoL? Aim 2: Describe the relationship between SCD self-management strategies and QoL. Significance: Understanding the relationships between perceived stigma, demographic and clinical characteristics, SCD self-management strategies and QoL in Jamaica and the US will illuminate useful comparisons that could lead to new strategies to improve SCD self-management despite stigma.